28,703 research outputs found

    Human papillomavirus E2 regulates SRSF3 (SRp20) to promote capsid protein expression in infected differentiated keratinocytes

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    The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the infected epithelial cell suggesting a sophisticated interplay between host cell metabolism and virus replication. Previously we demonstrated in differentiated keratinocytes in vitro and in vivo that HPV16 infection caused increased levels of the cellular SR splicing factors (SRSFs) SRSF1 (ASF/SF2), SRSF2 (SC35) and SRSF3 (SRp20). Moreover, the viral E2 transcription and replication factor that is expressed at high levels in differentiating keratinocytes could bind and control activity of the SRSF1 gene promoter. Here we reveal that E2 proteins of HPV16 and HPV31 control expression of SRSFs 1, 2 and 3 in a differentiation-dependent manner. E2 has the greatest trans-activation effect on expression of SRSF3. siRNA depletion experiments in two different models of the HPV16 life cycle (W12E and NIKS16) and one model of the HPV31 life cycle (CIN612-9E) revealed that only SRSF3 contributed significantly to regulation of late events in the virus life cycle. Increased levels of SRSF3 are required for L1 mRNA and capsid protein expression. Capsid protein expression was regulated specifically by SRSF3 and appeared independent of other SRSFs. Taken together these data suggest a significant role of the HPV E2 protein in regulating late events in the HPV life cycle through transcriptional regulation of SRSF3 expression. IMPORTANCE Human papillomavirus replication is accomplished in concert with differentiation of the infected epithelium. Virus capsid protein expression is confined to the upper epithelial layers so as to avoid immune detection. In this study we demonstrate that the viral E2 transcription factor activates the promoter of the cellular SRSF3 RNA processing factor. SRSF3 is required for expression of the E4̂L1 mRNA and so controls expression of the HPV L1 capsid protein. Thus we reveal a new dimension of virus-host interaction crucial for production of infectious virus. SRSF proteins are known drug targets. Therefore, this study provides an excellent basis for developing strategies to regulate capsid protein production in the infected epithelium and production of new virions

    Positive Operator-Valued Measure reconstruction of a beam-splitter tree based photon-number-resolving detector

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    Here we present a reconstruction of the Positive Operator-Value Measurement of a photon-number-resolving detector comprised of three 50:50 beamsplitters in a tree configuration, terminated with four single-photon avalanche detectors. The four detectors' outputs are processed by an electronic board that discriminates detected photon number states from 0 to 4 and implements a "smart counting" routine to compensate for dead time issues at high count rates

    Quantum Statistical Calculations and Symplectic Corrector Algorithms

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    The quantum partition function at finite temperature requires computing the trace of the imaginary time propagator. For numerical and Monte Carlo calculations, the propagator is usually split into its kinetic and potential parts. A higher order splitting will result in a higher order convergent algorithm. At imaginary time, the kinetic energy propagator is usually the diffusion Greens function. Since diffusion cannot be simulated backward in time, the splitting must maintain the positivity of all intermediate time steps. However, since the trace is invariant under similarity transformations of the propagator, one can use this freedom to "correct" the split propagator to higher order. This use of similarity transforms classically give rises to symplectic corrector algorithms. The split propagator is the symplectic kernel and the similarity transformation is the corrector. This work proves a generalization of the Sheng-Suzuki theorem: no positive time step propagators with only kinetic and potential operators can be corrected beyond second order. Second order forward propagators can have fourth order traces only with the inclusion of an additional commutator. We give detailed derivations of four forward correctable second order propagators and their minimal correctors.Comment: 9 pages, no figure, corrected typos, mostly missing right bracket

    A new scenario for string unification

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    We present a new scenario for gauge coupling unification in flipped SU(5) string models, which identifies the M32M_{32} scale of SU(3) and SU(2) unification with the empirical MLEP101516M_{\rm LEP}\sim10^{15-16}~GeV scale, and the M51M_{51} scale of SU(5) and U(1) unification with the theoretical Mstring5×1017M_{\rm string}\sim5\times10^{17}~GeV string unification scale. The vacuum shift necessary for the cancellation of the anomalous UA(1)\rm U_A(1) and an SU(4) hidden sector with fractionally-charged particles, play a crucial role in the dynamical determination of all intermediate mass scales in this scenario.Comment: 8 pages, LaTeX, 2 figures (uuencoded

    Self-energy correction to the hyperfine structure splitting of the 1s and 2s states in hydrogenlike ions

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    The one-loop self-energy correction to the hyperfine structure splitting of the 1s and 2s states of hydrogenlike ions is calculated both for the point and finite nucleus. The results of the calculation are combined with other corrections to find the ground state hyperfine splitting in lithiumlike ^{209}Bi^{80+} and ^{165}Ho^{64+}.Comment: The table 2 is changed. 6 pages, 1 figure, Late

    Transition energy and lifetime for the ground state hyperfine splitting of high Z lithiumlike ions

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    The ground state hyperfine splitting values and the transition probabilities between the hyperfine structure components of high Z lithiumlike ions are calculated in the range Z=4983Z=49-83. The relativistic, nuclear, QED and interelectronic interaction corrections are taken into account. It is found that the Bohr-Weisskopf effect can be eliminated in a combination of the hyperfine splitting values of the hydrogenlike and lithiumlike ions of an isotope. This gives a possibility for testing the QED effects in a combination of the strong electric and magnetic fields of the heavy nucleus. Using the experimental result for the 1s1s hyperfine splitting in ^{209}Bi^{82+}, the 2s hyperfine splitting in ^{209}Bi^{80+} is calculated to be \Delta E=0.7969(2) eV.Comment: The nuclear charge distribution correction \delta is corrected, 14 pages, Late

    The detection of ultra-relativistic electrons in low Earth orbit

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    Aims. To better understand the radiation environment in low Earth orbit (LEO), the analysis of in-situ observations of a variety of particles, at different atmospheric heights, and in a wide range of energies, is needed. Methods. We present an analysis of energetic particles, indirectly detected by the Large Yield RAdiometer (LYRA) instrument on board ESA's Project for On-board Autonomy 2 (PROBA2) satellite as background signal. Combining Energetic Particle Telescope (EPT) observations with LYRA data for an overlapping period of time, we identified these particles as electrons with an energy range of 2 to 8 MeV. Results. The observed events are strongly correlated to geo-magnetic activity and appear even during modest disturbances. They are also well confined geographically within the L=4-6 McIlwain zone, which makes it possible to identify their source. Conclusions. Although highly energetic particles are commonly perturbing data acquisition of space instruments, we show in this work that ultra-relativistic electrons with energies in the range of 2-8 MeV are detected only at high latitudes, while not present in the South Atlantic Anomaly region.Comment: Topical Issue: Flares, CMEs and SEPs and their space weather impacts; 20 pages; 7 figures; Presented during 13th European Space Weather Week, 201
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